{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T18:44:50Z","timestamp":1789670690597,"version":"4.0.1"},"reference-count":28,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,4,15]],"date-time":"2026-04-15T00:00:00Z","timestamp":1776211200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004826","name":"Beijing Natural Science Foundation","doi-asserted-by":"publisher","award":["7224328"],"award-info":[{"award-number":["7224328"]}],"id":[{"id":"10.13039\/501100004826","id-type":"DOI","asserted-by":"publisher"}]},{"name":"China CDC-Tuberculosis Control and Prevention Project","award":["2428"],"award-info":[{"award-number":["2428"]}]},{"DOI":"10.13039\/501100012166","name":"National Key R&D Program of China","doi-asserted-by":"crossref","award":["2023YFC2307301"],"award-info":[{"award-number":["2023YFC2307301"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100012166","name":"National Key R&D Program of China","doi-asserted-by":"crossref","award":["2022YFC2305204"],"award-info":[{"award-number":["2022YFC2305204"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Med."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Digital droplet PCR (ddPCR) offers high sensitivity and absolute quantification without standard curves, making it promising for tuberculosis (TB) detection in paucibacillary samples. This study evaluated the diagnostic performance of a ddPCR assay targeting IS6110 and 23S rRNA for pulmonary tuberculosis (PTB) and tuberculous pleurisy (TP).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>A total of 436 patients (245 suspected PTB, 191 suspected TP) were prospectively enrolled. ddPCR was performed on sputum, bronchoalveolar lavage fluid, and pleural effusion samples. Diagnostic performance was compared with Xpert MTB\/RIF and culture.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      In suspected PTB, ddPCR showed significantly higher sensitivity than Xpert (49.70% vs. 38.10%,\n                      <jats:italic>p<\/jats:italic>\n                      &amp;lt; 0.001), while Xpert showed higher specificity (98.65% vs. 87.70%). In suspected TP, ddPCR also demonstrated superior sensitivity (17.54% vs. 10.40%,\n                      <jats:italic>p<\/jats:italic>\n                      &amp;lt; 0.001). For NTM detection, ddPCR achieved 60% sensitivity and 99.58% specificity.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>ddPCR offers improved sensitivity for PTB and TP diagnosis, particularly in paucibacillary cases, though its lower specificity necessitates confirmatory testing. The dual-target design enables simultaneous MTB\/NTM differentiation, providing clinical utility for guiding appropriate therapy.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fmed.2026.1819767","type":"journal-article","created":{"date-parts":[[2026,4,15]],"date-time":"2026-04-15T04:45:10Z","timestamp":1776228310000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["Evaluation of a new droplet digital PCR for diagnosis of pulmonary tuberculosis and tuberculous pleurisy"],"prefix":"10.3389","volume":"13","author":[{"given":"Xichao","family":"Ou","sequence":"first","affiliation":[{"name":"National Key Laboratory of Intelligent Tracking and Forecasting for Infectious Diseases, National Center for Tuberculosis Control and Prevention, Chinese Centre for Disease Control and Prevention","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huiwen","family":"Zheng","sequence":"additional","affiliation":[{"name":"Beijing Key Laboratory of Pediatric Respiratory Infection Diseases, Key Laboratory of Major Diseases in Children, Ministry of Education, National Clinical Research Center for Respiratory Diseases, Laboratory of Respiratory Diseases, Beijing Pediatric Research Institute, Beijing Children\u2019s Hospital, Capital Medical University, National Center for Children\u2019s Health","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xundi","family":"Bao","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory, Anhui Chest Hospital","place":["Hefei, China"]},{"name":"Anhui Provincial Center for Disease Control and Prevention","place":["Hefei, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peilei","family":"Hu","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory, Hunan Chest Hospital","place":["Changsha, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhou","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory, Anhui Chest Hospital","place":["Hefei, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingwei","family":"Guo","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory, Hunan Chest Hospital","place":["Changsha, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dongfang","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory, Anhui Chest Hospital","place":["Hefei, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yue","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory, Anhui Chest Hospital","place":["Hefei, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingjing","family":"Li","sequence":"additional","affiliation":[{"name":"Beijing Key Laboratory of Pediatric Respiratory Infection Diseases, Key Laboratory of Major Diseases in Children, Ministry of Education, National Clinical Research Center for Respiratory Diseases, Laboratory of Respiratory Diseases, Beijing Pediatric Research Institute, Beijing Children\u2019s Hospital, Capital Medical University, National Center for Children\u2019s Health","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bing","family":"Zhao","sequence":"additional","affiliation":[{"name":"National Key Laboratory of Intelligent Tracking and Forecasting for Infectious Diseases, National Center for Tuberculosis Control and Prevention, Chinese Centre for Disease Control and Prevention","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Kang","sequence":"additional","affiliation":[{"name":"Beijing Key Laboratory of Pediatric Respiratory Infection Diseases, Key Laboratory of Major Diseases in Children, Ministry of Education, National Clinical Research Center for Respiratory Diseases, Laboratory of Respiratory Diseases, Beijing Pediatric Research Institute, Beijing Children\u2019s Hospital, Capital Medical University, National Center for Children\u2019s Health","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qi","family":"Ma","sequence":"additional","affiliation":[{"name":"Beijing Key Laboratory of Pediatric Respiratory Infection Diseases, Key Laboratory of Major Diseases in Children, Ministry of Education, National Clinical Research Center for Respiratory Diseases, Laboratory of Respiratory Diseases, Beijing Pediatric Research Institute, Beijing Children\u2019s Hospital, Capital Medical University, National Center for Children\u2019s Health","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui","family":"Xia","sequence":"additional","affiliation":[{"name":"National Key Laboratory of Intelligent Tracking and Forecasting for Infectious Diseases, National Center for Tuberculosis Control and Prevention, Chinese Centre for Disease Control and Prevention","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yunhong","family":"Tan","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory, Hunan Chest Hospital","place":["Changsha, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanlin","family":"Zhao","sequence":"additional","affiliation":[{"name":"National Key Laboratory of Intelligent Tracking and Forecasting for Infectious Diseases, National Center for Tuberculosis Control and Prevention, Chinese Centre for Disease Control and Prevention","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,4,15]]},"reference":[{"key":"ref1","volume-title":"Global Tuberculosis Report","year":"2023"},{"key":"ref2","doi-asserted-by":"publisher","first-page":"e0237753","DOI":"10.1371\/journal.pone.0237753","article-title":"The epidemiology of extrapulmonary tuberculosis in China: a large-scale multi-center observational study","volume":"15","author":"Kang","year":"2020","journal-title":"PLoS One"},{"key":"ref3","doi-asserted-by":"publisher","first-page":"106607","DOI":"10.1016\/j.rmed.2021.106607","article-title":"Diagnosis of tuberculous pleural effusions: a review","volume":"188","author":"Lo Cascio","year":"2021","journal-title":"Respir Med"},{"key":"ref4","doi-asserted-by":"publisher","first-page":"1243441","DOI":"10.3389\/fcimb.2023.1243441","article-title":"Diagnostic accuracy and microbial profiles of tuberculous pleurisy: a comparative study of metagenomic next generation sequencing and GeneXpert Mycobacterium tuberculosis","volume":"13","author":"Huang","year":"2023","journal-title":"Front Cell Infect Microbiol"},{"key":"ref5","doi-asserted-by":"publisher","first-page":"962","DOI":"10.1111\/resp.13673","article-title":"Tuberculous pleural effusion","volume":"24","author":"Shaw","year":"2019","journal-title":"Respirology"},{"key":"ref6","doi-asserted-by":"publisher","first-page":"1216339","DOI":"10.3389\/fcimb.2023.1216339","article-title":"ddPCR provides a sensitive test compared with GeneXpert MTB\/RIF and mNGS for suspected Mycobacterium tuberculosis infection","volume":"13","author":"Zhang","year":"2023","journal-title":"Front Cell Infect Microbiol"},{"key":"ref7","volume-title":"Global Tuberculosis Report","year":"2021"},{"key":"ref8","doi-asserted-by":"publisher","first-page":"2100526","DOI":"10.1183\/13993003.00526-2021","article-title":"A prospective multicentre diagnostic accuracy study for the Truenat tuberculosis assays","volume":"58","author":"Penn-Nicholson","year":"2021","journal-title":"Eur Respir J"},{"key":"ref9","doi-asserted-by":"publisher","first-page":"435","DOI":"10.1183\/09031936.00007814","article-title":"Xpert MTB\/RIF assay for the diagnosis of extrapulmonary tuberculosis: a systematic review and meta-analysis","volume":"44","author":"Denkinger","year":"2014","journal-title":"Eur Respir J"},{"key":"ref10","doi-asserted-by":"publisher","first-page":"268","DOI":"10.1016\/j.chest.2019.07.027","article-title":"Accuracy of Xpert MTB\/RIF ultra for the diagnosis of pleural TB in a multicenter cohort study","volume":"157","author":"Wang","year":"2020","journal-title":"Chest"},{"key":"ref11","doi-asserted-by":"publisher","first-page":"e33","DOI":"10.52225\/narraj.v1i2.33","article-title":"Diagnostic performance of GeneXpert MTB\/RIF assay compared to conventional Mycobacterium tuberculosis culture for diagnosis of pulmonary and extrapulmonary tuberculosis, Nepal","volume":"1","author":"Chaudhary","year":"2021","journal-title":"Narra J"},{"key":"ref12","doi-asserted-by":"publisher","first-page":"41","DOI":"10.1586\/14737159.4.1.41","article-title":"Principle and applications of digital PCR","volume":"4","author":"Pohl","year":"2004","journal-title":"Expert Rev Mol Diagn"},{"key":"ref13","doi-asserted-by":"publisher","first-page":"85","DOI":"10.1016\/j.tube.2019.07.001","article-title":"Droplet digital PCR applications in the tuberculosis world","volume":"117","author":"Nyaruaba","year":"2019","journal-title":"Tuberculosis"},{"key":"ref14","doi-asserted-by":"publisher","first-page":"727774","DOI":"10.3389\/fmicb.2021.727774","article-title":"Rapid detection and quantification of Mycobacterium tuberculosis DNA in paraffinized samples by droplet digital PCR: a preliminary study","volume":"12","author":"Antonello","year":"2021","journal-title":"Front Microbiol"},{"key":"ref15","volume-title":"Definitions and Reporting Framework for Tuberculosis\u20142013 Revision: Updated December 2014 and January 2020","year":"2013"},{"key":"ref16","doi-asserted-by":"publisher","first-page":"e7","DOI":"10.52225\/narrarev.v1i2.7","article-title":"Machine learning-based algorithms for early detection of tuberculosis: a scoping review","volume":"1","author":"Ramadhan","year":"2025","journal-title":"Narra Rev"},{"key":"ref17","doi-asserted-by":"publisher","first-page":"942.e1","DOI":"10.1016\/j.cmi.2019.11.012","article-title":"A novel approach for tuberculosis diagnosis using exosomal DNA and droplet digital PCR","volume":"26","author":"Cho","year":"2020","journal-title":"Clin Microbiol Infect"},{"key":"ref18","doi-asserted-by":"publisher","first-page":"47","DOI":"10.1016\/j.tube.2016.04.004","article-title":"Digital PCR assay detection of circulating Mycobacterium tuberculosis DNA in pulmonary tuberculosis patient plasma","volume":"99","author":"Ushio","year":"2016","journal-title":"Tuberculosis"},{"key":"ref19","doi-asserted-by":"publisher","first-page":"537","DOI":"10.1038\/31159","article-title":"Deciphering the biology of Mycobacterium tuberculosis from the complete genome sequence","volume":"393","author":"Cole","year":"1998","journal-title":"Nature"},{"key":"ref20","doi-asserted-by":"publisher","first-page":"373","DOI":"10.1016\/S0167-7012(03)00070-8","article-title":"Sequence analysis in the 23S rDNA region of Mycobacterium tuberculosis and related species","volume":"54","author":"Kurabachew","year":"2003","journal-title":"J Microbiol Methods"},{"key":"ref21","doi-asserted-by":"publisher","first-page":"745","DOI":"10.4014\/jmb.1409.09089","article-title":"A simple, single triplex PCR of IS6110, IS1081, and 23S ribosomal DNA targets, developed for rapid detection and discrimination of Mycobacterium from clinical samples","volume":"25","author":"Nghiem","year":"2015","journal-title":"J Microbiol Biotechnol"},{"key":"ref22","doi-asserted-by":"publisher","first-page":"1615","DOI":"10.1128\/jcm.31.6.1615-1618.1993","article-title":"Characterization of Mycobacterium tuberculosis strains from Vietnamese patients by southern blot hybridization","volume":"31","author":"Yuen","year":"1993","journal-title":"J Clin Microbiol"},{"key":"ref23","doi-asserted-by":"publisher","first-page":"109","DOI":"10.1016\/S0962-8479(98)80003-8","article-title":"Differences in the prevalence of IS6110 insertion sites in Mycobacterium tuberculosis strains: low and high copy number of IS6110","volume":"78","author":"Fomukong","year":"1997","journal-title":"Tuber Lung Dis"},{"key":"ref24","doi-asserted-by":"publisher","first-page":"1310","DOI":"10.3201\/eid0811.020291","article-title":"Molecular differentiation of Mycobacterium tuberculosis strains without IS6110 insertions","volume":"8","author":"Lok","year":"2002","journal-title":"Emerg Infect Dis"},{"key":"ref25","doi-asserted-by":"publisher","first-page":"820","DOI":"10.1016\/j.ijid.2022.07.041","article-title":"A new droplet digital PCR assay: improving detection of paucibacillary smear-negative pulmonary tuberculosis","volume":"122","author":"Zhao","year":"2022","journal-title":"Int J Infect Dis"},{"key":"ref26","doi-asserted-by":"publisher","first-page":"e0163222","DOI":"10.1128\/spectrum.01632-22","article-title":"Use of pleural fluid digital PCR analysis to improve the diagnosis of pleural tuberculosis","volume":"10","author":"Li","year":"2022","journal-title":"Microbiol Spectrum"},{"key":"ref27","doi-asserted-by":"publisher","first-page":"1900250","DOI":"10.1183\/13993003.00250-2019","article-title":"Non-tuberculous mycobacterial pulmonary disease","volume":"54","author":"Cowman","year":"2019","journal-title":"Eur Respir J"},{"key":"ref28","doi-asserted-by":"publisher","first-page":"e178","DOI":"10.1016\/S1473-3099(21)00586-7","article-title":"Consensus management recommendations for less common non-tuberculous mycobacterial pulmonary diseases","volume":"22","author":"Lange","year":"2022","journal-title":"Lancet Infect Dis"}],"container-title":["Frontiers in Medicine"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmed.2026.1819767\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,15]],"date-time":"2026-04-15T04:45:17Z","timestamp":1776228317000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmed.2026.1819767\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4,15]]},"references-count":28,"alternative-id":["10.3389\/fmed.2026.1819767"],"URL":"https:\/\/doi.org\/10.3389\/fmed.2026.1819767","relation":{},"ISSN":["2296-858X"],"issn-type":[{"value":"2296-858X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,4,15]]},"article-number":"1819767"}}